Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer: lessons learned and future directions

Abstract

Poly (ADP-ribose) polymerase inhibitors (PARPi) represent a new standard of care in the upfront treatment of advanced epithelial ovarian cancer to the point that the vast majority of patients now receive a PARPi, alone or in combination with the anti-angiogenic bevacizumab, as part of their first-line maintenance therapy. The clinical benefit of PARPi is well established; however, much has changed since their introduction and several relevant questions have been raised and remain unresolved in the post-PARPi era. The decision-making process regarding the most appropriate first-line maintenance therapy could be challenging in clinical practice, especially in the homologous recombination-proficient setting, and several other factors need to be considered apart from the mutational status. Concerns regarding post-PARPi progression treatment have emerged, highlighting an unmet need to define a valid algorithm strategy. PARPi may not only compromise the response to further platinum due to cross-resistance mechanisms but the impact on subsequent non-platinum chemotherapy and surgery also remains unclear. Definitive results on the role of PARPi rechallenge are awaited, especially in the case of oligoprogression managed with locoregional treatment. Moreover, the updated overall survival data from the recurrent setting warrant caution in using PARPi as single agents for unselected patients. Several PARPi combination regimens are emerging for overcoming PARPi resistance and may become our new therapeutic armamentarium. This review discusses a set of clinically relevant issues in the PARPi era and provides a glimpse of future challenges and opportunities in ovarian cancer treatment.

MITO39: Efficacy and Tolerability of Pegylated Liposomal Doxorubicin (PLD)–Trabectedin in the Treatment of Relapsed Ovarian Cancer after Maintenance Therapy with PARP Inhibitors—A Multicenter Italian Trial in Ovarian Cancer Observational Case-Control Study

“…Currently, there are a variety of possible approaches to a patient who progresses on or after PARP inhibitors [ 12 , 12 ]. Although a solid therapeutic algorithm is still missing, the use of loco-regional treatments such as surgical intervention or radiotherapy (RT) and the continuation of PARP inhibitors therapy is widely spread in oligo-metastatic progression, with data so far coming only from retrospective evidence alone [ 13 , 14 ]; therefore, the validation of this approach through a randomized prospective trial is needed.…”

The role of inflammatory factors and T‐cell subsets in the diagnosis of recurrence in epithelial ovarian cancer patients and the effect of olaparin treatment on them

“…Inclusion criteria were as follows: (1) the patient was diagnosed with ovarian epithelial carcinoma through clinical, imaging, and pathological tests; (2) Federation International of Gynecology and Obstetrics (FIGO) is divided into Stages III or IV; (3) the patient's age is between 18 and 70 years old; (4) the patient receives chemotherapy treatment for this disease for the first time; (5) all patients underwent tumor cell reduction surgery; and ( 6) the patient has no other malignant tumors. Exclusion criteria were as follows:…”

“…However, maintenance treatment has not been really implemented in clinic for a long time, and maintenance treatment is not encouraged for patients with ovarian cancer, mainly because of serious drug toxicity and side effects or little survival benefit. Until the emergence of anti angiogenesis drugs and molecular targeted drugs such as poly‐adenosine diphosphate ribose polymerase inhibitor (PARPi), the current situation of maintenance treatment of ovarian cancer has been really improved 5,6 . The establishment of maintenance therapy for ovarian cancer has changed the previous treatment mode and strategy of ovarian cancer, and provided new hope for improving the poor prognosis of ovarian cancer.…”

PARP inhibitor era: current status and future directions

“…Caruso and colleagues nicely detail the clinical narrative for ovarian cancer treatment in the era of anti-angiogenesis and poly (ADP-ribose) polymerase inhibitor (PARPi) therapy. 1 The authors outline a clinical decision algorithm based on results from recent trials, molecular annotation, and emerging science, describing probabilistic models of innate and acquired drug resistance. As is clearly presented, the next wave of clinical trials will be prospectively addressing important hypotheses raised from these initial observations in an attempt to better define treatment strategies that optimize care.…”

“…Caruso and colleagues nicely detail the clinical narrative for ovarian cancer treatment in the era of anti-angiogenesis and poly (ADP-ribose) polymerase inhibitor (PARPi) therapy 1. The authors outline a clinical decision algorithm based on results from recent trials, molecular annotation, and emerging science, describing probabilistic models of innate and acquired drug resistance.…”